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Content archived on 2024-05-30

Systematic dissection of molecular machines and neural circuits coordinating C. elegans aggregation behaviour

Objective

Elucidating how neural circuits coordinate behaviour, and how molecules underpin the properties of individual neurons are major goals of neuroscience. Optogenetics and neural imaging combined with the powerful genetics and well-described nervous system of C. elegans offer special opportunities to address these questions. Previously, we identified a series of sensory neurons that modulate aggregation of C. elegans. These include neurons that respond to O2, CO2, noxious cues, satiety state, and pheromones. We propose to take our analysis to the next level by dissecting how, in mechanistic molecular terms, these distributed inputs modify the activity of populations of interneurons and motoneurons to coordinate group formation. Our strategy is to develop new, highly parallel approaches to replace the traditional piecemeal analysis.

We propose to:
1) Harness next generation sequencing (NGS) to forward genetics, rapidly to identify a molecular ¿parts list¿ for aggregation. Much of the genetics has been done: we have identified almost 200 mutations that inhibit or enhance aggregation but otherwise show no overt phenotype. A pilot study of 50 of these mutations suggests they identify dozens of genes not previously implicated in aggregation. NGS will allow us to molecularly identify these genes in a few months, providing multiple entry points to study molecular and circuitry mechanisms for behaviour.
2) Develop new methods to image the activity of populations of neurons in immobilized and freely moving animals, using genetically encoded indicators such as the calcium sensor cameleon and the voltage indicator mermaid.

This will be the first time a complex behaviour has been dissected in this way. We expect to identify novel conserved molecular and circuitry mechanisms.

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Topic(s)

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Call for proposal

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ERC-2010-AdG_20100317
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Funding Scheme

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ERC-AG - ERC Advanced Grant

Host institution

MEDICAL RESEARCH COUNCIL
EU contribution
€ 2 439 996,00
Address
20 Park Crescent
W1B 1AL LONDON
United Kingdom

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Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
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Total cost

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Beneficiaries (1)

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